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The Abdi Lab  is interested in understanding the molecular mechanisms underlying pain and related neuropathology involved in cancer, with multidisciplinary approaches and tools including immunohistochemistry, protein expression, electrophysiology (patch-clamp recording), mammalian cell culture and animal models. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, significantly impacting patients' quality of life. Despite advances in chemotherapy, current treatments for CIPN¡ªsuch as opioids, antiepileptics, and antidepressants¡ªare often ineffective or associated with serious side effects. Nonpharmacologic approaches like TENS, acupuncture, and yoga show mixed results. Recently, scrambler therapy (ST), a noninvasive electrocutaneous stimulation technique, has emerged as a promising alternative for managing CIPN. The Abdi Lab¡¯s hypothesis is that ST can effectively reduce pain, improve neuropathy, and enhance quality of life in patients with CIPN. Preliminary studies have also highlighted the potential of other novel treatments, including reactive oxygen species (ROS) scavengers, PDE4 inhibitors, and Wnt blockers, in alleviating CIPN symptoms. Further investigation of these therapies is warranted to identify effective, safer alternatives to current pharmacologic treatments for CIPN. Grants include:

• NIH/NCI - R21 CA256136 | S Abdi (PI)     
  • 02/2022 ¨C 01/2025
  • Innovative Treatment of Chemotherapy-Induced Painful Peripheral Neuropathy in Adolescents and Young Adults with Cancer: A two arm pilot study  

• NIH/NCI - R01 CA245054 | S Abdi (Co-I)
  • 06/2021 ¨C 05/2024
  • Auricular Point Acupressure to Manage Chemotherapy Induced Neuropathy   

• WEX Pharmaceuticals Inc ¨C 2022-1010 | S Abdi (Site PI) 
  • 05/2024 ¨C 04/2025
  • A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain 
    

The Cata Laboratory is dedicated to deciphering the role of mu-opioid receptor signaling in head and neck squamous cell carcinoma. In 2014, Cata founded the Anesthesiology and Surgical Oncology Research Group. His group is focused on translational and clinical research and is dedicated to investigating the mechanisms of perioperative immune suppression and opioid-mediated tumor progression. This work has clear implications for the survival of our patients as each impact the ability for micro-metastases to seed and survive in the peri-operative period. Additionally, he is heavily involved with perioperative symptom management and enhanced recovery after surgery (ERAS). This includes collaborative projects focusing on gynecologic, thoracic, spine and head and neck surgeries as well as a basic laboratory research program. He has several funded clinical trials and has published more than 220 peer-reviewed publications. Grants include:

• NIH/NIDA - R42 DA050365 | Christina York (Contact PI), J Cata (MPI), Van Meter (Co-I), Huh (Co-I) 
  • 08/2020 ¨C 8/2024 
  • An augmented reality platform to reduce post-operative and chronic opioid use in pediatric cancer   

• NIH/NIDA - R43 DA057744 | Christina York (Contact PI), J Cata (MPI) 
  • 09/2022 -9/2023 
  • Feasibility of a dual English/Spanish mobile augmented reality pain assessment app to reduce postoperative prescription opioid use in Hispanic/Latino pediatric and adolescent cancer patients   

• NIH/NCI - UH3 CA261067 | J Cata (Site PI) 
  • 09/2022 ¨C 08/2025 
  • Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain (KALPAS)   

• PCORI - SUBK00020601 | J Cata (Site PI) 
  • 07/2023 ¨C 06/2025 
  • THRIVE: Trajectories of Recovery after Intravenous propofol vs inhaled VolatilE Anesthesia   

• Peter McCallum Cancer Institute ¨C 2020-0002 | J Cata (Site PI) 
  • 03/2023 ¨C 4/2024 
  • Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial   

• Bausch Healthcare US,LLC ¨C 2021-0845 | J Cata (PI) 
  • 11/2023 ¨C 11/2025 
  • Methylnatrexone In resectable head aNd necK squamous cell carcinoma. The MINK pilot study   

• Merck ¨C MISP101548 | J Cata (PI) 
  • 10/2023 ¨C 10/2025 
  • A retrospective study to compare the association between Sugammadex vs Neostigmine on return to intended oncological therapy   

• Haisco Pharma ¨C 2023-0701 | J Cata (Site PI) 
  • 01/2024 ¨C 12/2024 
  • Global multicenter, randomized, double blinded, propofol controlled, phase 3 to evaluate the efficacy and safety of HSK3486   

• Haisco Pharma ¨C 2022-1075 | J Cata (Site PI) 
  • 04/2023 ¨C 9/2023 
  • A Multicenter, Randomized, Double-blinded, Propofol-controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HSK3486 Injectable Emulsion for Induction of General Anesthesia in Adults undergoing Elective Surgery 

The Dougherty Lab examines mechanisms of chronic pain, including neuropathic pain related to metastasized cancer and chemotherapy-induced peripheral neuropathy. We conduct physiological, biochemical and anatomical studies using both rodent and human nervous tissue. Our research focuses on chemotherapy-induced neuropathy using rodent models and an in vitro human dorsal root ganglion (DRG) culture system, with a unique approach of utilizing human sensory neurons collected during spinal surgery for metastatic tumor treatment. In collaboration with Lifegift, an organ procurement organization, we have developed procedures for collecting human DRG tissue from organ donors within hours of cross-clamp, ensuring minimal ischemic time. This enables comparison of sensory neurons from healthy controls and MD Anderson cancer patients to study neuropathic pain mechanisms. This work has contributed to the creation of a Tissue Procurement and Processing Core, supported by a U19 grant and in partnership with the University of Texas at Dallas and University of Washington. Ongoing studies using DRG tissue from MD Anderson patients have revealed significant sex differences in RNA expression in dermatomes with and without radiculopathy, guiding further investigation into pain mechanisms, such as cytokine oncostatin-M (OSM). We have found that OSM upregulation in pain-associated DRGs sensitizes neurons and decreases mechanical withdrawal thresholds, highlighting potential therapeutic targets like the MNK1/2-eIF4E signaling axis. Additionally, collaborations with UC San Diego investigate the role of TLR4 lipid rafts in neuroinflammation, using a novel TLR4-depleting compound (AIBP) to reduce nociceptive behavior and spontaneous neuronal activity. These studies are supported by a multi-PI R01 grant to explore potential interventions for chronic pain. Grants include:

• NIH/NINDS - R01 NS111929 | P Dougherty (PI) 
  • 04/2020 ¨C 2/2026  
  • Anatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRG   

• NIH/NINDS - U19 NS130608 | T Price (Contact PI), P Dougherty (MPI) 
  • 09/2022 ¨C 08/2027 
  • Human Nociceptor and Spinal Cord Molecular Signature Center   

• NIH/NINDS - R01 NS132483 | T Yaksh (Contact PI), P Dougherty (MPI) 
  • 07/2024 ¨C 12/2028 
  • Role of TLR4-lipid rafts in nociception   

• NIH/NINDS - R42 NS132622 | P Dougherty (Contact PI)
  • 09/2023 ¨C 8/2025 
  • Targeting TLR4-lipid rafts to prevent postoperative pain   

• NIH/NINDS - R01 NS065926 | T Price (PI), P Dougherty (Co-I) 
  • 03/2019 ¨C 1/2025 
  • Translational Control of Pain Plasticity   

• NIH/NINR - R01 NR018481 | A Viswanathan (PI), Dougherty (Co-I) 
  • 06/2019 ¨C 02/2025 
  • Percutaneous Cordotomy for Pain Palliation in Advanced Cancer   

• NIH/NCI - R37 CA242006 | A Moran (PI), Dougherty (Co-I) 
  • 06/2020 ¨C 05/2025 
  • Defining the Role of Tumor-Neural Crosstalk in head and Neck Cancer Progression and Treatment Resistance 

The Pan laboratory focuses on neuroscience research, specifically the function of voltage- and ligand-gated ion channels and synaptic plasticity in chronic pain, opioid actions, and neurogenic hypertension. Our current studies include: (1) neural circuitry and molecular mechanisms of chronic neuropathic pain caused by cancer chemotherapy, surgery, and nerve trauma; (2) signaling transduction mechanisms involved in opioid-induced hyperalgesia and analgesic tolerance; and (3) roles of the hypothalamus and sympathetic nervous system in neurogenic hypertension caused by chronic stress and clinically used medications.  Grants include:

• NIH/NHLBI - R01 HL154512 | HL Pan (PI) 
  • 08/2020 ¨C 07/2025 
  • Neural Mechanisms of Calcineurin Inhibitor-Induced Hypertension   

• NIH/NIDA - R01 DA041711 | HL Pan (PI), Shao-Rui Chen (MPI) 
  • 03/2017 ¨C 04/2027 
  • Signaling Mechanisms of Opioid-Induced Hyperalgesia and Tolerance

• NIH/NINDS - R01 NS101880 | HL Pan (PI), Shao-Rui Chen (MPI) 
  • 08/2017 ¨C 11/2027 
  • Molecular Determinants of Synaptic Plasticity in Neuropathic Pain   

• NIH/NINDS - R01 NS132398 | HL Pan (PI), Shao-Rui Chen (MPI) 
  • 04/2023 ¨C 03/2028 
  • Mechanisms of Epigenetic Plasticity in Neuropathic Pain   

• NIH/NINDS - R01 NS112280 | Sadhan Majumder (contact PI), HL Pan (MPI) 
  • 09/01/2019 ¨C 07/30/2024 
  • REST-Mediated Epigenomic and Transcriptomic Signatures in Neuropathic Pain   

• NIH/NIDA ¨C R66/33 DA049334 | Sadhan Majumder (contact PI), HL Pan (MPI) 
  • 07/01/2020 ¨C 06/30/2027 
  • REST-Mediated Regulation of Opioid Receptors in Chronic Pain Mouse Models   

• NIH/NIDCR - R01 DE032501 | Yi Ye (PI), HL Pan (Co-I) 
  • 9/2022 ¨C 08/2027 
  • Targeting HB-EGF and trigeminal EGFR for oral cancer pain and opioid tolerance   

The Pan ZZ lab  has advanced our understanding of chronic pain through epigenetic mechanisms, identifying specific modifications in histone acetylation and DNA methylation that affect genes like Gad65 and Ngf, which are crucial for GABA function and opioid sensitivity. These epigenetic changes offer insights into the development of chronic pain and its increased sensitivity to opioids. Additionally, the lab's research has highlighted how persistent pain enhances opioid sensitivity by modulating shared molecular pathways, leading to heightened responses to pain and opioids, a critical factor in opioid abuse potential and pain management. Further contributions from the lab focus on the synaptic plasticity of glutamate receptors, particularly within the central amygdala, and how chronic pain and opioid exposure alter synaptic circuits involved in reward and emotion. Using optogenetics, they have identified two distinct brain circuits in the central amygdala with opposing effects on pain and emotion: the parabrachial nucleus (PBN)-to-CeA pathway, which promotes negative emotional behaviors without affecting pain sensitivity, and the basolateral amygdala (BLA)-to-CeA pathway, which counteracts these emotions and inhibits pain. These findings suggest a top-down brain mechanism for cognitive control of pain and emotion under chronic pain conditions, revealing potential therapeutic targets for modulating both pain and emotional responses in patients. Grants include:

• NIH/NINDS - RF1 NS113256 | ZZ Pan (PI) 
  • 09/2019 ¨C 8/2024 
  • Dnmt3a as an epigenetic target for chronic pain treatment   

• NIH/NIDA - R01 DA056673 | L Li (PI), ZZ Pan (Co-I) 
  • 12/2022 ¨C 11/2027 
  • Targeting Tiam1-mediated synaptic plasticity for relief of opioid tolerance  

•  DOD - HT94252410686 | ZZ Pan (PI)
  • 08/2024 ¨C 07/2028 
  • Cortical and amygdala circuits mechanisms for chronic pain 

The Sharma Lab is currently focusing on neutrophil differentiation and mechanistic understanding of reactive oxygen species (ROS)- and autophagy-activated NET formation. In this regard, they have discovered the role of innate immune C-type lectin receptor Mincle, ROS sensor calcium channel protein TRPM2 and NLRP3 inflammasome as central regulators of autophagy-independent, and ROS-dependent NET formation respectively (PMID: 28186242, 35768151, 29906250, 39186692). Furthermore, the lab has found that breast cancer drug tamoxifen can potentiate NETs in CGD patient neutrophils (PMID: 31039377); while PARP-1 inhibitors can block NETs in inflammatory conditions (PMID: 39186692). Because NETs are implicated in tumor progression and metastasis, yet their role in endocrine therapy resistance in breast cancer patient is unexplored, these studies will provide therapeutic opportunities to prevent cancer metastasis and cancer drug resistance. Lastly, they have identified unique NET-associated signatures that we are testing as diagnostic and predictive markers for disease severity in microbial infections and sepsis. Grants include: 

• NIH/NIAID - R01 AI155582 | J Sharma (PI) 
  • 03/2021 - 02/2026  
  • Neutrophil Extracellular Traps and Host Immunity 

• NIH/NCI - R21 CA274085 | J Sharma (PI)  
  • 04/2024 ¨C 03/2026  
  • Impact of tamoxifen treatment on neutrophils in breast cancer patients 

• VolitionRx - 2021-1171 | J Sharma (PI), I Malik (Co-I)  
  • 02/2023 - 04/2025
  • Correlation of circulating NETs and cell-free DNA with inflammatory immune responses in Cancer patients with sepsis 

• NIH/NIAID - R01 AI164721 | Mishra (Contact PI), Sharma (MPI)
  • 08/2021 - 07/2025 
  • Lung Macrophage Memory Development and Responses in Secondary Pneumonia and Sepsis 

The Yan Lab aims to elucidate the composition, structure, and function of ion channel signaling complexes. He is particularly interested in identifying novel protein targets, molecular mechanisms, and modulators for ion channel-targeted drug discovery and therapeutics. Currently, his lab works on: (1) identifying new ion channel regulatory proteins using mass spectrometry-based proteomics; (2) unraveling the physiological and pathological roles of ion channel auxiliary proteins in pain, ataxia, anxiety, depression, and cognition using rodent models; (3) determining the 3D atomic structures of ion channel signaling complexes using cryogenic electron microscopy; and (4) screening therapeutic compounds that target the interactions between ion channels and their regulatory proteins. Grants include:

• NIH/NINDS - R01 NS078152 | J Yan (PI) 
  • 08/2012 ¨C 08/2024 
  • BK Channel Regulation by Auxiliary LRR Proteins   

• NIH/NIGMS - R01 GM130814 | J Yan (PI) 
  • 09/2018 ¨C 07/2026 
  • Molecular Basis of the NAADP-gated Calcium Release Channel Complexes   

• NIH/NIGMS - R01 GM130814-S1 | J Yan 
  • 08/2023 ¨C 7/2024 
  • Supplement_Molecular Basis of the NAADP-gated Calcium Release Channel Complexes